This laboratory has long been interested in the role of enterically derived endotoxin in the initiation and perpetuation of liver injury, mechanisms involved in the process, and the effect of modifying endotoxicity on the extent of experimental hepatic damage. Work in this area has been hampered in the past by the lack of an endotoxin marker that could be used to quantitate endotoxemia. Our laboratory has developed an immunoradiometric assay (IRMA) for E. coli 026 that presently detects the specific LPS at a concentration as low as 10 ng/ml. The appearance, and amount of E. coli 026 in the circulation arising from oral administration of the LPS is being studied in a variety of acute and chronic rat liver injuries. In addition, the same technique is being used to develop an assay for lipid A, a shared endotoxin core in the hope of detecting heterologous endotoxins in the circulation. Presently, we are comparing the sensitivity of our immunoradiometric assay for E. coli 026 with both the limulus lysate assay and using I131 labelled LPS. As an extension of work completed, we propose to further investigate our initial observations on the kinetics of endotoxin absorption in the everted gut sac of normal rats and to study also, absorption in sacs from rats with acute and chronic liver injury. Using this model, the role of bile salts, pancreatic enzymes, pH and histamine in the absorption and detoxification of endotoxin will also be studied. Immunization studies using LPS from S. minnesota R 595 and its effect on endotoxin absorption both in vivo and vitro are also currently under study.